Computational Analysis using Multi-ligand Simultaneous Docking of Withaferin A and Garcinol Reveals Enhanced BCL-2 and AKT-1 Inhibition
Journal:
arXiv
Published Date:
May 13, 2025
Abstract
Developing an effective medicine to combat cancer and elusive stem cells is
crucial in the current scenario. Withaferin A and Garcinol, important
phytoconstituents of Withania somnifera (Ashwagandha) and Garcinia indica
(Kokum) respectively, known for their therapeutic efficiency, have been used
for several decades for treating various disorders, because of their
anti-cancerous, anti-inflammatory and anti-invasive properties. This study
investigates the potentials of withaferin A and garcinol in inhibiting BCL-2
and AKT-1, crucial proteins contributing in cancer cell persistence by evading
apoptosis, increased cell proliferation, and inflammation. Molecular docking
techniques, including single docking and MLSD, were used to understand the
binding interaction of the ligands with BCL-2 and AKT-1. MLSD highlighted
inter-ligand interactions among withaferin A and garcinol, against BCL-2, with
a binding affinity of -11.88 +- 0.12 kcal/mol, surpassing the binding affinity
of venetoclax (-9.73 +- 0.1 kcal/mol) a commercial inhibitor of BCL-2. For
AKT-1, the binding affinity of withaferin A and garcinol (-13.74 +- 0.08
kcal/mol) surpassed the binding affinity of melatonin (-7.24 +- 0.06 kcal/mol),
a commercial inhibitor of AKT-1. The MLSD results highlight the combined
effects of garcinol and withaferin A, highlighting the importance of
considering both the interactions of the bioactive compounds in the development
of new medicines and strategies targeting cancer and elusive stem cells.
